Our analysis of events in immediate hypersensitivity focuses on human and animal models of allergic responses, mechanisms of mediator action, and pharmacologic approaches to allergic diseases. The areas under investigation include asthma, allergic rhinitis, anaphylaxis, urticaria and mastocytosis. Histamine, one of the major mediators released by human lung, was shown to interact with 3 distinct H1 receptors on isolated human lung membranes. Similarly, histamine may react with two H1 receptors on purified human lymphocytes. It appears that infusions of dopamine may inhibit histamine skin reactivity; therefore, skin tests on patients receiving dopamine are invalid. The mechanism for narcotic induced mast cell degranulation was examined and found to involve both specific opiate receptors as well as receptor-independent mechanisms. Vascular permeability can be examined by measuring the leak of radiolabeled IgG or well-defined dextrans. The use of dextran permits analysis of vascular leakage over a long period and will facilitate study of microvascular events during cutaneous inflammatory reactions. Nasal allergic reactions involve rhinorrhea; therefore, a model for the study of nasal secretions in humans in vivo was developed. Methacholine acting on muscarinic receptors stimulates mucus secretion and atopics are hyperresponsive compared to normal controls. As mast cells are the cellular midus of allergic reactions, depletion of mast cells might be a powerful method of therapy. Strategies for mast cell killing include IgE-ricin and IgE-ricin A chain. Both methods cause mast cell death.